It is proposed that studies be performed to further elucidate the mode of action of 3,4-dihydroxybutyl-1-phosphonate as it relates to metabolic regulation in general bacterial organisms. This drug, as an isosteric analogue of glycerol-3-phosphate, bears the potential of acting as a regulator in numerous systems. To the end of this aim, it is proposed that several specifically labeled forms of this compound be prepared and used in biochemical studies along with analogue of other phosphate intermediates of the metabolic pathways of the organisms of interest. We have shown one aspect of the action of this drug to involve modification of lipid composition. Further investigations are planned to examine membrane phenomena as they relate to the phosphonates. A major problem in the use of these analogues is that of transport into whole cells. We propose the attachment of the analogues to oligopeptides that they may enter the cells through known oligopeptide transport systems (illicit transport). These investigations are planned with prokaryotic cells initially, and then attempts will be made to extend the work to eukaryotic cells. New analogues of glycerol-3-phosphate are to be prepared in a continuing search for metabolic regulators. These will include phosphonates, sulfates, and sulfonates, as well as phosphate species of special interest. In this last category is L-glyceraldehyde-3-phosphate, which, in its hydrated (prominent) form, constitutes an analogue of glycerol-3-phosphate, and has been found to be of use by us for metabolic regulation. We propose to synthesize analogues of glycerol and glycerol-3-phosphate in the hope that they can be exploited as probes into basic metabolic processes and serve as chemotherapeutic agents.